Ketomalonic acid diesters are derivatives of malonic acid having a keto group, and are compounds to be important intermediates in an organic synthesis. In particular, ketomalonic acid diesters are useful compounds as raw materials in the production of pyrazine-2-one-3-carboxylic acid ester derivatives by the reaction with diamines (see Patent Documents 1 to 4 and Non Patent Documents 1 and 2). This reaction is utilized in the manufacture of pharmaceuticals, agricultural chemicals, and the like particularly as a method for producing quinoxalinone derivatives from aromatic diamines.
Conventionally, direct or indirect methods have been reported as the method of synthesizing ketomalonic acid diesters from malonic acid diesters. However, they all have a problem. As the method of a synthesizing ketomalonic acid diesters from malonic acid diesters, for example, a method is known in which a ketomalonic acid diester is produced by oxidizing a malonic acid diester with an oxidizing agent such as selenium dioxide (for example, see Non Patent Document 3), dinitrogen trioxide (for example, see Non Patent Document 4), or chromium trioxide (for example, see Non Patent Document 6). However, they also all have a problem such as severe toxicity of reagents, a difficulty in handling of reagents, and the like.
In addition, methods of producing a ketomalonic acid diester such as a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with bromine is reacted with silver nitrate (for example, see Non Patent Document 7), a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with an azo group is reacted with dimethyldioxirane (for example, see Non Patent Document 8), a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with a methylene group is reacted with ozone (for example, see Non Patent Documents 5 and 9), and a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with a hydroxyl group is reacted in the presence of a noble metal catalyst (for example, see Patent Document 5), and the like are also known. However, in these methods, there is a drawback that tartronic acid that is much more expensive than malonic acid diesters is used as a raw material or the active methylene moiety of a malonic acid diester is required to be modified in advance. Hence, these methods have economic and operational problems. In addition, these methods have a problem that expensive reagents, special reactants, expensive catalysts, or transition metals are used, or the like.
Furthermore, a method in which a malonic acid diester is reacted with a chlorite has been reported (see Patent Document 6). The method described in Patent Document 6 is superior to conventional methods known earlier than Patent Document 6, but it has been found out that it has a number of problems to be solved in order to implement the method on an industrial scale.